This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is connective tissue growth factor-2 sometimes hereinafter referred to as xe2x80x9cCTGF-2xe2x80x9d. The invention also relates to inhibiting the action of such polypeptides.
The CTGF polypeptides are structurally and functionally related to a family of growth factors which include IGF (insulin-like growth factor), PDGF (platelet-derived growth factor), and FGF (fibroblast growth factor). This emerging family of secreted proteins are a group of cysteine-rich proteins. This group of growth factors are important for normal growth, differentiation, morphogenesis of the cartilaginous skeleton of an embryo and cell growth. Among some of the functions that have been discovered for these growth factors are wound healing, tissue repair, implant fixation and stimulating increased bone mass.
The extended superfamily of growth factors include TGF (transforming growth factor), bone morphogenic factors, and activins, among others.
The most well-known growth factor, TGF exerts a number of different effects on a variety of cells. For example, TGF-xcex2 can inhibit the differentiation of certain cells of mesodermal origin (Florini, J. R. et al., J. Biol. Chem., 261:1659-16513 (1986) induced the differentiation of others (Seyedine, S. M. et al., PNAS USA, 82:2267-2271 (1987) and potently inhibit proliferation of various types of epithelial cells, (Tucker, R. F., Science, 226:705-705 (1984)). This last activity has led to the speculation that one important physiological role for TGF-xcex2 is to maintain the repressed growth state of many types of cells. Accordingly, cells that lose the ability to respond to TGF-xcex2 are more likely to exhibit uncontrolled growth and become tumorigenic.
Accordingly, due to amino acid sequence homology the polypeptide of the present invention is a member of this extended family of growth factors which has many effects on a variety of different tissues.
In accordance with one aspect of the present invention, there is provided a novel mature polypeptide, as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof. The polypeptide of the present invention is of human origin.
In accordance with another aspect of the present invention, there are provided isolated nucleic acid molecules encoding a polypeptide of the present invention including mRNAs, DNAS, cDNAs, genomic DNAs as well as analogs and biologically active and diagnostically or therapeutically useful fragments thereof.
In accordance with yet a further aspect of the present invention, there is provided a process for producing such polypeptide by recombinant techniques comprising culturing recombinant prokaryotic and/or eukaryotic host cells, containing a nucleic acid sequence encoding a polypeptide of the present invention, under conditions promoting expression of said protein and subsequent recovery of said protein.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptide, or polynucleotide encoding such polypeptide for therapeutic purposes, for example, enhancing the repair of connective and support tissue, promoting the attachment, fixation and stabilization of tissue implants and enhancing wound healing.
In accordance with yet a further aspect of the present invention, there are provided antibodies against such polypeptides.
In accordance with yet a further aspect of the present invention, there is also provided nucleic acid probes comprising nucleic acid molecules of sufficient length to specifically hybridize to a nucleic acid sequence of the present invention.
In accordance with yet a further aspect of the present invention, there are provided antibodies against such polypeptides.
In accordance with another aspect of the present invention, there are provided agonists which mimic the polypeptide of the present invention and binds to the receptors.
In accordance with yet another aspect of the present invention, there are provided antagonists to such polypeptides, which may be used to inhibit the action of such polypeptides, for example, in the treatment of CTGF dependent tumor growth.
In accordance with still another aspect of the present invention, there are provided diagnostic assays for detecting diseases or susceptibility to diseases related to mutations in the nucleic acid sequences encoding a polypeptide of the present invention.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides, for in vitro purposes related to scientific research, for example, synthesis of DNA and manufacture of DNA vectors.
These and other aspects of the present invention should be apparent to those skilled in the art from the teachings herein.